Internalization of carcinogenic lead chromate particles by cultured normalhuman lung epithelial cells: Formation of intracellular lead-inclusion bodies and induction of apoptosis

Occupational exposure to certain particulate hexavalent chromium [Cr(VI)] c ompounds, such as lead chromate, has been associated with lung cancer and r espiratory tract toxicity. We have previously shown that apoptosis is a maj or mode of death in cultured rodent cells treated with soluble sodium chrom ate and particulate lead chromate. Here we report the cellular and molecula r effects of lead chromate and sodium chromate in normal human lung small a irway epithelial (HSAE) cells, which may be one of the targets for Cr(VI)-i nduced lung cancer and respiratory tract toxicity. Phagocytosed lead chroma te particles and intracellular lead-inclusion bodies (LIB) were observed by transmission electron microscopy and confirmed by X-ray analysis. HSAE cel ls exposed to lead chromate and sodium chromate underwent dose-dependent ap optosis. The cellular uptake and genomic interactions of both Cr and lead ( Pb) were examined by inductively coupled plasma mass spectrometry (ICPMS) c oupled with a novel, direct-injection high-efficiency nebulizer (DIHEN). Us ing this approach, we have quantitated a dose-dependent formation of Cr-DNA adducts and DNA-associated Pb in lead chromate-treated HSAE cells. The for mation of LIE in normal human lung cells exposed to lead chromate indicates that ionic Pb is released from the particles and thus might contribute to the cell toxicity caused by lead chromate. Internalization and dissolution of lead chromate particles and the interaction of ionic Cr and Pb with DNA, may be components of the mechanism of lead chromate carcinogenesis. Lead c hromate-induced apoptosis may be a mechanism to eliminate cells with chromi um- and/or lead-damaged DNA. (C) 1999 Academic Press.